Immunocytochemical investigation of Langerin (CD207) is a valuable adjunct in the cytological diagnosis of Langerhans cell histiocytosis of the thyroid

Langerhans cell histiocytosis (LCH) is an uncommon disease encompassing three clinically different entities: eosinophilic granuloma, Hand-Schüller-Christian disease, and Abt-Letterer-Siewe disease. Despite usually being a multisystemic disease affecting numerous different organs, involvement of the thyroid gland is extremely rare, and only a few cases in adults have been described in the literature. Herein, we present the case of a 28-year-old male patient presenting with LCH involving the skin, the skeletal system, and the thyroid gland. Fine needle aspiration (FNA) of the thyroid was performed and showed the typical Langerhans cells (LC) with foamy cytoplasm and slender nuclei with longitudinal grooves against a background of inflammatory cells with only a few eosinophilic granulocytes. Immunocytochemically, the LC showed positive staining with antibodies against CD1a and Langerin, a recently detected glycoprotein exclusively expressed in LC. Langerin is the major protein that makes up the so-called Birbeck granules, the electronmicroscopical hallmark of LC. Since LCH involvement of the thyroid is occasionally mistaken for papillary thyroid carcinoma cells, we propose that application of Langerin in combination with CD1a is a helpful diagnostic adjunct for the correct assessment of LCH affecting the thyroid gland.     

慢性淋巴细胞性甲状腺炎伴TRAb阴性的甲状腺相关性眼病1例

甲状腺相关性眼病是一种自身免疫系统紊乱引起的眼球后及眶周组织的浸润性病变,常与Graves病并存或先后发病,但慢性淋巴细胞性甲状腺炎中甲状腺相关性眼病较罕见。本文报告1例促甲状腺素受体抗体(TRAb)阴性,细针穿刺活检示弥漫性淋巴细胞浸润,符合慢性淋巴细胞性甲状腺炎相关性眼病的诊断病例。     

The pathogenetic connection between Graves' disease and chronic lymphocytic thyroiditis. (The role and incidence of thyroid stimulating antibodies)

Antibody-positivity to thyroid specific antigens (Htg, microsomal) and/or lymphocytic infiltration of the gland's parenchyma were observed in 207 (55%) of 377 patients with Graves's disease. Only in 48 (12.7%) of the cases were the findings in agreement with the criteria of chronic lymphocytic thyroiditis. Human thyroid stimulating antibody (HTSab) was detected in 135 (65%) of these 207 patients. In cases of Graves' disease associated with chronic lymphocytic thyroiditis, this proportion was found to be as high as 89.6% and attained even 100% in cases of Hashitoxicosis (39 patients). The presence of HTSab thus seems to form one of the features of patients with Hashitoxicosis. Infiltrative ophthalmopathy also showed a remarkably high incidence (59%) in this porcess. The typical prevalence of Graves' disease in females in the present material attained a 15:1 female-to-male ratio when the disease was associated with chronic lymphocytic thyroiditis. The results of the present study suggest that chronic lymphocytic thyroiditis associated with Graves' disease promotes the formation of thyroid stimulating antibodies.     

An unusual presentation of primary lymphoma of the thyroid in a young male patient

Primary lymphoma of the thyroid gland is a rare disease that is strongly associated with chronic lymphocytic thyroiditis. We report an unusual case of 20-year-old male who presented with thyroid swelling and was diagnosed on cytology as lymphocytic thyroidtis. However, histopathologicalfindings revealed non-Hodgkin's lymphoma that was further classified as B-cell type on immunohistochemical stains. In cytology, lymphomas must be considered as a differential diagnosis in case of Hashimoto's/lymphocytic thyroiditis, subacute thyroiditis and small cell carcinoma.     

Expression of tenascin in lymphocytic autoimmune thyroiditis.

AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all activated lymph follicles with germinal centres. This staining pattern contrasted with the immunoreactions for collagen III and IV, which were not enhanced in the perilymphofollicular interstitium. In cases of thyroiditis DeQuervain the areas of early and ongoing fibrosis showed some diffuse staining for tenascin and for collagen III. Enhanced diffuse immunostaining for collagen IV in the perivascular and interfollicular interstitium was present in cases of Grave's disease. In Grave's disease no characteristic immunoreaction was detectable for tenascin. CONCLUSIONS: The corona-like expression of tenascin around lymphofollicular infiltrates is distinctive of cases of lymphocytic thyroiditis. A similar staining pattern for tenascin has been reported in lymphoid hyperplasia of the thymus associated with myasthenia gravis, another autoimmunological disorder. There are good arguments that the activation and infiltration of lymph follicles in the thyroid during the course of autoimmune diseases lead to stimulation and activation of the surrounding mesenchyme producing tenascin as part of the extracellular matrix.     

Granulomatous and lymphocytic thyroiditis associated with a follicular adenoma

A 44-year-old woman came to medical attention with right thyroid lobe enlargement and weight loss. Thyroid scan and ultrasound demonstrated a nodule in the right thyroid lobe; a right hemithyroidectomy was performed. Histologic examination documented granulomatous and lymphocytic thyroiditis associated with a follicular adenoma. No inflammation was apparent within the adenoma. The parallels between granulomatous thyroiditis and lymphocytic thyroiditis, including presumed viral initiation and deranged immunologic function, suggest that granulomatous thyroiditis may evolve into chronic lymphocytic thyroiditis; this case may be an example of such a transition. It is proposed that thyroid follicular adenomas have different antigenicity, which may account for the conspicuous absence of inflammation within the tumor.     

Lithium associated autoimmune thyroiditis.

A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration. Some areas showed a moderate degree of stromal fibrosis and atrophic thyroid follicles. Lymphoid follicles with germinal centres, disrupted thyroid follicles with lymphocytic infiltration, and Hürthle cells were also observed. The differential diagnosis in patients presenting with these histological features includes painless (silent) thyroiditis, autoimmune thyroiditis and lithium associated autoimmune thyroiditis. A detailed clinical history is essential if the correct diagnosis is to be reached.     

Postpartum silent thyroiditis simulating a malignant lymphoma of the thyroid

A case of postpartum silent thyroiditis simulating a malignant lymphoma of the thyroid is reported. The patient was a 30-yr-old female who had received irradiation thearapy to the neck for malignant lymphoma of the thyroid 9 yr previously. She was referred to our department because of a struma associated with acute aggravation of chronic thyroiditis after parturition. In this case, the mechanism of the disease was explained by the “immune rebound hypothesis”. It was difficult to differentiate postpartum silent thyroiditis from malignant lymphoma of the thyroid, either clinically or cytologically, when the immune-rebound phenomenon with lymphocytic infiltration and the appearance of lymphoid follicles were prominent. The immunological status of patients with chronic thyroiditis accompanied by morphological changes should be taken into consideration before establishing the diagnosis of malignant lymphoma of the thyroid.     

Lymphoepithelial cysts of the thyroid gland. A case report and review of the literature

We report a case of multiple lymphoepithelial cysts of the thyroid gland in a patient with severe chronic lymphocytic thyroiditis. Lymphoepithelial cysts of the thyroid gland are rare lesions that are histologically similar to branchial cleft cysts found in the lateral neck. The cysts have an epithelial lining that is usually stratified squamous epithelium but may be focally respiratory-type epithelium. Abundant lymphoid tissue is present beneath the epithelium, and lymphoid follicles with reactive germinal centers are common features in the walls of the cysts. Because of their similarity to branchial cleft cysts and the presence of intrathyroidal branchiae-derived structures such as thymus and parathyroid gland tissue in the vicinity of some cysts, lymphoepithelial cysts of the thyroid have been postulated to arise from remnants of branchial derivatives; origination from solid cell nest remnants of the ultimobranchial bodies has been raised as a possibility. A definitive origin, however, has not been established. An association with chronic thyroiditis has been noted in 8 of the previously reported 16 cases occurring in a background of Hashimoto or chronic lymphocytic thyroiditis.     

Focal lymphocytic thyroiditis in Southampton

The presence of focal collections of lymphocytes within the thyroid gland has been associated with autoimmune thyroiditis. In a prospective study 197 thyroid glands were examined from post mortems performed in two Southampton hospitals over a 12 month period. The mean thyroid mass was 19.5 g in women and 22.2 g in men. Varying degrees of focal lymphocytic thyroiditis were present in 54 per cent of women and 24 per cent of men. Morphometry showed that on average less than 4 per cent of the gland was infiltrated by lymphocytes. There was no significant relationship with age. A possible association between focal lymphocytic thyroiditis and circulating thyroid autoantibodies has been shown.     

Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis)

Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T-cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution.     

Hashimoto's thyroiditis as a risk factor of thyroid lymphoma

Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle-aged women. Histologic features of Hashimoto's thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16-23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohistologic studies revealed that all of the thyroid lymphomas were of the B-cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sj?gren syndrome and rheumatoid arthritis have also been reported to be B-cell derived. Therefore it is suggested that immune deficiency is a causal factor for B-cell lymphoma.     

The association between chronic lymphocytic thyroiditis and thyroid tumors

An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.     

Investigation of the clonality of lymphocytes in Hashimoto's thyroiditis using immunoglobulin and T-cell receptor gene probes

Southern blotting and DNA hybridization were used for the detection of immunoglobulin and T-cell receptor gene rearrangements in thyroid tissue from six patients with Hashimoto's thyroiditis, three patients with B-cell lymphoma complicating Hashimoto's thyroiditis, and two patients with nonspecific lymphocytic thyroiditis. Immunoglobulin gene rearrangements were detected only in patients with histologic evidence of lymphoma. A single T-cell receptor beta-chain gene rearrangement was detected in one of the patients with uncomplicated Hashimoto's thyroiditis. Based on our knowledge of primary thyroid lymphomas, it is highly unlikely that this case represents an early, histologically occult T-cell lymphoma. The uniform lack of immunoglobulin gene rearrangements in Hashimoto's thyroiditis supports the use of genotypic analysis in differentiating between uncomplicated Hashimoto's thyroiditis and non-Hodgkin's lymphoma. The finding of a T-cell receptor gene rearrangement in a case of Hashimoto's thyroiditis suggests that the immune response in this disease occasionally may be clonally restricted.     

Up-regulation of cyclooxygenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase

To cast light on relations of cyclooxygenase-2 (COX-2) expression to lymphocytic thyroiditis and thyroid tumorigenesis, protein levels were immunohistochemically assessed and compared with inducible nitric oxide synthase (iNOS) in a total of 181 cases: follicular adenoma, 23; well-differentiated papillary carcinoma, 85; poorly differentiated papillary carcinoma, 25; anaplastic carcinoma, 7; and follicular carcinoma, 41. In addition, 72 specimens of normal follicular epithelia and 36 of lymphocytic thyroiditis were used as control samples. Immunohistochemical results were confirmed in 2 cases each of normal thyroid, lymphocytic thyroiditis, and well-differentiated and poorly differentiated papillary carcinoma, by Western blotting assay. Stepwise increments in overexpression of COX-2 and iNOS were revealed in epithelial cells of lymphocytic thyroiditis, follicular adenoma, and papillary carcinoma; normal thyroid epithelium showed little expression. A significant positive correlation between the 2 enzymes was found with all cases. Enhanced expression of both COX-2 and iNOS suggests important roles in the inflammatory processes underlying lymphocytic thyroiditis and thyroid tumorigenesis.     

Optimalization of methodical repertoire for laboratory diagnostic of autoimune diseases of the thyroid gland--aspiration cytology versus histology (cytodiagnostic accuracy)

In this study was evaluated the rate of cytodiagnostic accuracy of Hashimoto's thyroiditis (HT) in smears prepared from thyroid fine-needle aspirates in 72 cases and of focal lymphocytic thyroiditis (FLT) in 101 cases. The cytodiagnostic accuracy of Hashimoto's thyroiditis (HT) was 75% and 20% in case of focal lymphocytic thyroiditis (FLT). In case of focal lymphocytic thyroiditis (FLT) the cytodiagnostics of autoimmune lymphocytic diseases of thyroid gland apears to have very low ability.     

Hashimoto’s thyroiditis: TGAb,TPOAb, TRAb and recovery from hypothyroidism

Hashimoto described four patients with goiter. The histology of the goiter was characterized by diffuse lymphocytic infiltration, fibrosis and epithelial cell destruction. Thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) have been used to diagnose Hashimoto’s thyroiditis. Patients with positive TGAb and/or TPOAb have been assumed to have Hashimoto’s thyroiditis. Approximately 10% of those with positive TGAb and/or TPOAb have hypothyroidism. There are two types of autoimmune thyroiditis: goitrous Hashimoto’s thyroiditis and atrophic thyroiditis. The latter patients have blocking antibody (thyroid-stimulating hormone [TSH]-stimulation blocking antibody [TSBAb]). TSBAb is a TSH-receptor antibody (TRAb). TSBAb causes thyroid atrophy and hypothyroidism. TGAb and/or TPOAb do not necessarily cause hypothyroidism. Hypothyroid patients with Hashimoto’s thyroiditis usually receive life-long l-thyroxine therapy. However, spontaneous recovery from hypothyroidism has been reported. Patients who had Hashimoto’s hypothyroidism and then Graves’ hyperthyroidism (and vice versa), have also been reported. Hashimoto’s hypothyroidism and Graves’ hyperthyroidism could be the opposite spectrums of one disease.     

甲状腺粘膜相关淋巴瘤与淋巴细胞性甲状腺炎的临床病理及免疫组化研究

报道甲状腺粘膜相关淋巴瘤１２例，淋巴性甲状腺炎６例。淋巴性甲状腺炎分为轻、中、重三级。研究上述１８例有免疫组化结果的资料，发现粘膜相关淋巴瘤多见于老年女性，并从淋巴细胞性甲状腺炎发展演变而来，以中心细胞样细胞为多见，免疫组化示Ｂ－细胞性单克隆性。组织病理学上常形成淋巴上皮病变，瘤栓样或戒指样结构。本文探讨了淋巴性甲状腺炎与甲状腺粘膜相关淋巴瘤的发病机理、鉴别诊断及治疗方法的选择等。     

The familial occurrence of lymphocytic thyroiditis in borzoi dogs

A group of related borzoi dogs were studied over a 6-year period to ascertain the cause of primary hypothyroidism. Four generations of dogs were analyzed. Two littermates with lymphocytic thyroiditis were mated and the 10 offspring were all diagnosed, on the basis of thyroid biopsy evaluation, as having lymphocytic thyroiditis by age 2.5 years. A wide range of thyroid gland lesions was demonstrated in this litter of dogs. This report documents the occurrence of lymphocytic thyroiditis in three successive generations of an inbred group of borzoi dogs. An autosomal recessive mode of inheritance for the trait in this group of dogs is proposed.